Is there a late onset form of ADHD?

Philip Asherson MRCPsych, PhD

Professor of Molecular Psychiatry & Honorary
Consultant Psychiatrist,
MRC Social Genetic Developmental Psychiatry,
Institute of Psychiatry, UK

MRC Social Genetic and

Developmental Psychiatry
 Diagnostic criteria
What is ADHD
A persistent pattern of inattention and/or
hyperactivity-impulsivity that interferes with
functioning or development

What is not ADHD

The symptoms are not solely a manifestation of
oppositional behaviour, defiance, hostility, or
failure to understand tasks of instructions

American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, 2013
 Criteria for Adult ADHD Diagnosis: DSM-5

Hyperactivity
Inattention  Fidgetiness b(hands or feet) or squirming in
seat
 Lack of attention to details, makes careless
 Leaves seat when not supposed to
mistakes
 Restless or overactive
 Difficulty sustaining attention
 Difficulty engaging in leisure activities
 Does not listen when spoken to directly quietly
 Trouble completing or finishing job tasks  Always ‘on the go’
 Problems organizing tasks and activities  Talks excessively
 Avoids or dislikes sustained mental effort
Impulsivity
 Loses and misplaces things
 Blurts out answers before questions have
 Easily distracted been completed
 Forgetful in daily activities  Difficulty waiting in line or taking turns
 Interrupts or intrudes on others when they
are working or busy

American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition
2013
 DSM-5: Age-appropriate descriptions of ADHD

Inattention
• Mind elsewhere in the absence of obvious distractions
• Starts tasks, quickly loses focus, easily side-tracked
• Fails to finish tasks in the workplace
• Reporting task unrelated thoughts (mind wandering)
• Problems returning calls, paying bills
• Poor time management, not meeting deadlines
Hyperactivity
• Feeling restless
• Feeling uncomfortable being sat in restaurants or meetings
Impulsivity
• Butting into conversations or activities
• Intrude into and take over what other people are doing
American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013
Defining Adult ADHD (DSM-5)
● Criteria A: 5 or more symptoms of inattention or
hyperactivity-impulsivity

● Criteria B: Several symptoms present by the age of 12

● Criteria C: Several symptoms present in two or more settings

● Criteria D: Symptoms interfere with or reduce quality of social,

educational or occupational functioning

● Criteria E: Symptoms are not better explained by another

condition, such as mood disorder

American Psychiatric Association. Diagnostic and Statistical Manual (DSM) of Mental Disorders. 5th Edition 2013
 Domains of ‘IMPAIRMENT’
1. *Work Functions Psychosocial
2. *Social relationships
Psychiatric
3. *Coping with daily activities
4. Driving accidents (increased mortality) Neurodevelopmental
5. *Behavioural problems
6. *Distress from the symptoms
7. *Low self-esteem
(* NICE definition of impairment 2008)
8. Emotional instability
9. Sleep problems
10.*Risk for comorbid disorders (substance abuse, anxiety, depression,
personality disorder)
11. Cognitive impairments, including general and specific learning
difficulties (dyslexia, dyspraxia, autism spectrum disorder)

NICE Clinical Guideline 72. 2008. http://guidance.nice.org.uk/cg72;

Asherson P, Expert Rev Neurotherapeutics. 2005 Jul;5(4):525-39.
6
 Population prevalence rates

5.29%
Polanczyk et al 2007
 Prevalence of ADHD in children
14 13.3 12.9
p 12

e 10 8.8
r 8 7.1
c 6.1 5.7 5.9
6
e
4
n
t 2

DSM_IV subtype Prevalence Male : Female

Combined 3.4 2.7 : 1
Inattentive 1.8 1.8 : 1
Hyper-imp 0.8 3.5 : 1

Willcutt Neurotherapeutics (2012) 9: 490-499

Assuming 5% prevalence of ADHD during middle childhood and
50% decline every 5 years
• Estimated prevalence age 20 = 0.84%
• Estimated prevalence age 30 = 0.21%
• Estimated prevalence age 50 = 0.01%

Hill and Schoener

 Developmental delay

ADHD symptoms

ADHD

NORMAL

5 10 15

AGE
 Developmental deficit

Does ADHD persist?

ADHD symptoms

ADHD

NORMAL

5 10 15

AGE
ADHD symptom scores at 7 and 17 years

ADHD

Age 17 years
Age 7 years

Control

0 0.2 0.4 0.6 0.8 1 1.2

Scores from PACAS interview Taylor et al. 1996

The age-dependent decline and persistence of attention-
deficit/ hyperactivity disorder throughout the lifetime

Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder

Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
 Estimates of adult ADHD prevalence
based on longitudinal follow-up studies

Faraone meta-analysis 2006

• Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%

• In partial remission: 5% x 0.65 = 3.3%

 Prevalence of ADHD from US National
Comorbidity Survey
• Six symptoms of either inattention or hyperactivity-
impulsivity during last 6 months (A)
• Two or more symptoms before age 7 (B)
• Some impairment in at least two areas of living during
the past 6 months (C)
• Clinically significant impairment in at least one of these
areas (D).

Estimated prevalence of 4.4%

Kessler et al 2006, AmJPsych

 Prevalence of adult ADHD
TOTAL 3.4%
USA 5.2%
Spain 1.2%
Netherlands 5%
Mexico 1.9%
Lebanon 1.8%
Italy 2.8%
Germany 3.1%
France 7.3%
Colombia 1.9%
Belgium 4.1%
0 1 2 3 4 5 6 7 8

Fayyad et al., Br J Psychiatry. 2007 May;190:402-9.

 Prevalence of adult ADHD

• Prevalence = 2.5% (95% CI: 2.1–3.1%)

Simon et al. Br J Psychiatry. 2009 Mar;194(3):204-11

 Estimates of adult ADHD prevalence
based on longitudinal follow-up studies

Faraone meta-analysis 2006

• Full diagnosis of DSM-IV ADHD: 5% x 0.15 = 0.75%

• In partial remission: 5% x 0.65 = 3.3%

 Potential problems with
studies so far
• Child ADHD studies: clinical samples
influenced by referral bias

• Adult ADHD studies: depend on

retrospective recall
Dunedin Longitudinal Outcome Study

Child ADHD: follow-forward

Adult ADHD: follow-back
 Dunedin Child ADHD diagnosis
n=61 (6% of sample)
• DSM-III diagnoses established in 1984 – 1988
• Assessments by child psychiatrists (age 11-13)
and researchers (age 15) using DISC
• Parent/teacher ratings at ages 11, 13 and 15
• 8 or more symptoms rated by two sources (2/3
of cases) or one source (1/3 of cases)
• Onset before the age of 7 years
 Dunedin Adult’ ADHD diagnosis
n=31 (3% of the sample)
• Assessments in 2010-2012 aged 38
• Structured diagnostic interview with clinically trained
research staff
• Based on behaviour/symptoms in last 12 months
• Blind to prior data
• DSM-5 criteria applied
• Included age adjustments (e.g. difficulty sitting
through meetings, feeling restless)
• Informant ratings for childhood and adulthood
 6% of the total
sample met child
ADHD diagnosis

5% met adult ADHD

criteria
 6% of the total 3% of the total
sample met child sample met adult
ADHD diagnosis ADHD diagnosis

5% met adult ADHD 10% met child ADHD

criteria criteria
 Child onset ADHD vs Adult onset ADHD
Child ADHD Adult ADHD
(n=61, 6%) (n=31, 3%)

% male 87.7% (p<.001) 61.3% (ns)

Cognitive impairments in YES (p<.001) NO (ns)
childhood
Cognitive impairments in YES (p<.001) NO (ns)
adulthood
Associated with ADHD genetic YES (p=.04) NO (ns)
risk score
Life impairment at the age of 38 Yes (p<.001) Yes (p<.001)
 Questions
(1) Do children with ADHD grow out of the
disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset

condition that is distinct from childhood
ADHD?
 Questions
(1) Do children with ADHD grow out of the
disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset

condition that is distinct from childhood
ADHD?
 Number of ADHD symptoms reported by adults at age 38 years

INATTENTION

Child ADHD
group

Adult ADHD
group

Moffitt et al., 2015 Am J Psychiatry

 Number of ADHD symptoms reported by adults at age 38 years

INATTENTION HYPER-IMPULSIVITY

Child ADHD
group

Adult ADHD
group

Moffitt et al., 2015 Am J Psychiatry

 Parent report for ADHD symptoms at
the age of 38
1
Inattention

0.8
Hyperactivity-
impulsivity
0.6

0.4
Both p<.001

0.2

-0.2
Controls Child ADHD Adult ADHD

Moffitt et al., 2015 Am J Psychiatry

 Do children with ADHD grow out of
the disorder by adulthood?
NO
• Still cognitively impaired
• Still functionally impaired
• Still have high levels of ADHD symptoms
according to parents

The only inconsistent finding are ADHD

symptoms according to self-report

Moffitt et al., 2015 Am J Psychiatry

 Percentage persistence of children/adolescents with
DSM-IV ADHD: Follow-up period ~6.5 years
90
79
80
70
60
50
% 40
30
20
10
0
DSM-IV ADHD Combined Inattentive Hyper-imp Residual
subtype subtype subtype ADHD

• Mean age at baseline assessment = 11.8 (SD=2.9; range = 6-17)

• Mean age at follow-up assessment = 18.5 (SD=2.0; range = 12-26)

Cheung, Rijdijk, McLoughlin, Asherson, Kuntsi (2015) BJPsych, 2015

Self report leads to lower ADHD persistence rate
than parent report

ADHD ADHD ADHD

Persistent Remittent Persistence rate
(N) (N)
Parent 87 23 79%
report
Self report 48 60 44%

Du Rietz et al. 2016, J Psych Res

 Remittent vs Control Remitted vs Persistent
Parent Self Parent Self
IQ ✖ ✔ ✔ ✖
DSF ✖ ✔ ✖ ✖
DSB ✖ ✔ ✖ ✖
RTV ✖ ✔ ✔ ✔
OE ✖ ✔ ✔ ✖
CE ✖ ✔ ✖ ✖
CNV ✖ ✔ ✔ ✖
Cue-P3 ✖ ✖ ✖ ✖
Nogo-P3 ✖ ✔ ✖ ✖
Delta ✖ ✖ ✔ ✖
Theta ✖ ✖ ✔ ✖
Alpha ✖ ✔ ✖ ✖
Beta ✖ ✖ ✖ ✖
Movement Cheung et al. (2015)
intensity ✖ ✔ ✔ ✖ British Journal of
Psychiatry; Du Rietz et
Movement
✖ ✖ ✔ ✖ al. 2016, J Psych Res
count
 Remittent vs Control Remitted vs Persistent
Parent Self Parent Self
IQ ✖ ✔ ✔ ✖
DSF
Number of✖Neural and
✔ Cognitive
✖ markers✖ showing significant
DSB ✖ ✔ vs control
✖ differences
✖
group
RTV ✖ ✔ ✔ ✔
OE ✖ ✔ ✔ ✖
CE Parent rated ADHD Self rated ADHD
✖ ✔ ✖ ✖
CNV status status
✖ ✔ ✔ ✖
Cue-P3 ✖ ✖ ✖ ✖
Nogo-P3Persistent
✖ vs ✔ 8✖ ✖ 1
Delta remitted
✖ ✖ ✔ ✖
Theta Remitted
✖ vs ✖ 0✔ ✖ 10
Alpha controls
✖ ✔ ✖ ✖
Beta ✖ ✖ ✖ ✖
Movement Cheung et al. (2015)
intensity ✖ ✔ ✔ ✖ British Journal of
Psychiatry; Du Rietz et
Movement
✖ ✖ ✔ ✖ al. under review
count
Dynamic switching between task positive and
negative networks

Default mode network Salience network Executive control

Uddin L.Q. 2014, Nature Reviews Neuroscience

 Family studies
25
Risk to parents Risk to siblings
20
20

14.7
15
12.7

10

4.7
5
2.8
1.4

ADHD Control ADHD Control ADHD-CT Control

RR: 5.25 4.3 9.1

Faraone et al. 2000; Chen et al., NPG, 2008

 ADHD symptoms scores are
highly heritable

Boomsma 2003
Martin 2002
Kuntsi 2001
Coolidge 2000
Thapar 2000
Willcutt 2000
Hudziak 2000
Nadder 1998
Levy 1997
Sherman 1997
Silberg 1996
Gjone 1996
Thapar 1995
Schmitz 1995
Stevenson 1992
Edelbrock 1992
Gillis 1992
Goodman 1989
Matheny 1980
Willerman 1973

0 0.2 0.4 0.6 0.8 1

Heritability
 Monozygotic/Dizygotic twins:
Correlations for Teacher ADHD rating scales

0.9 DZtwins
MZ twins MZtwins
DZ twins
0.8
0.7
Correlations (r)

0.6
0.5
0.4
0.3
0.2
0.1
0

Identical twins (monozygotic): correlation ~ 76%

Non-identical twins (dizygotic): correlation ~ 35%

Asherson, unpublished data

New ADHD meta-analysis
18,284 cases 33,836 controls

10 loci
8 look robust
On the path!
 Adult twin studies
Phenotype Self-ratings Age Heritability

ADHD (study 1) Self 18-30 0.40

ADHD (study 2) Self 18+ 0.30

ADHD (study 3) Self 20-28 0.39

ADHD (study 3) Self 29-37 0.35

ADHD (study 3) Self 38-46 0.33

1. Van Den Berg et al. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(1):55-60;

2. Boomsma et al. 2010; PLoS ONE 5(5): e10621.
3. Larsson et al, JAMA Psychiatry 2011
 Heritability rates based on concordance rates for
ADHD diagnosis on Swedish national medical records

0.9
0.88
0.8
Heritability 0.72
0.7

0.6

0.5

0.4

0.3

0.2

0.1

Heritability overall Heritability in adults

Larsson et al., 2013, Psychological Medicine

 Questions
(1) Do children with ADHD grow out of the
disorder by the age of 38 years?

(2) Does ADHD in adults reflect an adult onset

condition that is distinct from childhood
ADHD?
 Two other population studies
UK study Brazil study
Age at ADHD 5 - 12 18 11 18-19
Number in sample 2232 4426
Prevalence of child ADHD 11% 8.9%
Prevalence of adult ADHD 7.4% 12.2%
% child ADHD with adult ADHD 21.9% 17.2%
% adult ADHD with child ADHD 67.5% 12.6%

ASSESSMENTS

Child assessment Parent or teacher Parent rated SDQ

reported ADHD
Adult assessment Participant interview Participant interview

Agnew-Blais, JAMA Psychiatry, 2016; Caye, JAMA Psychiatry, 2016

Is there an adult onset form of ADHD?

POSSIBLY but…..
- Rater effects: self-versus informant
- False positive paradox
- Neurodevelopmental origins - 1/3 had
oppositional defiant, conduct disorder or school
failure
- Subthreshold cases in childhood, with ADHD
emerging later in life
 70%

60%

50%

40%

30%

20%

10%

0%
7-9 years 7-12 years > 12 years

Late onset and full ADHD had similar patterns of:

- Impairment
- Psychiatric comorbidities
- Functional impairment
- Familial risks
Faraone et al., 2006, Am J Psych
 Bimodal distribution for self-reported age of onset of
adult ADHD symptoms in a population sample

SAIL Father SAIL Mother

Howe-Forbes, PhD, KCL, 2004

Possible causes of late onset ADHD
• Scaffolding during childhood/adolescence -
greater demands on ‘executive functioning’
• High IQ masking impairments
• Maturational delay/failure during adolescence
(e.g. executive control)
• Head injury
• Sleep disorders
• Toxins or drugs
Default Mode Network
 Words used to describe mind
wandering by adults with ADHD

My mind is:
Constantly daydreaming
In a fog
A whirlwind of thoughts
Hamster on a wheel
Jack in the box
Waves in a storm
Flitting and jumping
Asherson, Expert Review, 2005
Mind Wandering in ADHD
 “People with
Traffic noise Conversations Laughter
ADHD often
struggle with
filtering out”
Is it my fault Can I do my job Do you still
love me

Creativity Versatility Humour

 Components of Excessive Mind
Wandering in ADHD

• Thoughts on the go all the time

• Thoughts jumping of flitting from one

topic to another

• Multiple lines of thoughts at the same

time
 Sensitive to
Context regulation
reward
The decoupled brain: The brain does not detect sensory
visual and other stimuli during periods of mind wandering

Baird et al., 2014, J Cog Neurosci.

Performing
tasks
Performing
tasks

Inattentive
behaviour
Performing
tasks

Inattentive Sleep
behaviour problems
 Self-
Performing awareness
tasks and control
of behaviour

Inattentive Sleep
behaviour problems
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understand the relationship between
Creativity, Occupation, Mind wandering,
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Everyone’s mind wanders, but we all do it to a different degree, so

what is its impact?

tinyurl.com/mindwander
@FloMowlem
Contact: Florence Mowlem for more information
E-mail: florence.d.mowlem@kcl.ac.uk